Effect Of Atorvastatin On The Myocardial Protection In Diabetic Rabbits

Objective:To develop the rabbits models of diabetes mellitus(DM), to observe the changes of left ventricular diastolic function using tissue doppler imaging(TDI),to estimate the effect of Atorvastatin (Ato) on expression of transforming growth factorβ1(TGFβ1) in myocardium of diabetic rabbits,and to explore the possible mechanisms of Ato for the myocardial protection.Methods:Thirty-two Japanese Giant Ear Rabbits were randomly divided into 4 groups:A,normal control group;B,DM group;C,DM+low dose of Ato group(2mg/ kg.d);D,DM+high dose of Ato group(5mg/ kg.d). The rabbits models of diabetes mellitus were developed by alloxan, then given placebo or Ato intervention for twelve weeks. TDI technique was used to measure the early diastolic velocities(Em),late diastolic velocities (Am)and Em/Am ratio of mitral annuli in left lateral wall,left anterior wall,left inferior wall,left posterior wall,anterior septum and posterior septum.Blood glucose and serum lipids levels were detected.All rabbits were sacrificed at 12 weeks of diabetic duration. The weight of the whole heart and left ventricle were measured,which were used to calculate the ratio of heart weight to body weight (H/B) and the left ventricle mass index(LVMI),and the myocardial ultrastructure were observed by electron micro- scope.The expression of TGFβ1 was detected by immunohistochemistry.Results:(1)At 12 weeks of diabetic duration,alloxan-induced diabetic rabbits showed conspicuous myocardial ultrastructure,these results indicated the formation of diabetic cardiomyopathy.(2)At 12 weeks of diabetic duration,Compared with DM group, administration of Ato could significantly decrease serum TC and LDL-C in rabbits (dose dependent) (P< 0.01), TG greatly decreased and HDL-C increased in high dose of Ato group(P<0.05),but the changes of blood glucose were not significant in rabbits(P>0.05).(3)At 4 weeks of diabetic duration, Compared with normal control group, Em and Em/Am ratio of mitral annuli depressed in left ventricular wall of DM group and different dose of Ato group(P<0.05).There was no statistical significance between DM group and different dose of Ato group.(P>0.05).(4)At 8 weeks of diabetic duration,Compared with DM group and low dose of Ato group, Em and Em/Am ratio of mitral annuli significantly increased in left ventricular wall of high dose of Ato group(P < 0.05).There was no statistical significance between DM group and low dose of Ato group(P>0.05).(5)At 12 weeks of diabetic duration,Compared with DM group,Em and Em/Am ratio of mitral annuli significantly increased in left ventricular wall of high and low dose of Ato group(P<0.05).There was significal difference between high and low dose of Ato group(dose dependent)(P<0.05).(6)Compared with normal control group,myocardial expression of TGFβ1 increased significantly in DM group(P<0.01); Compared with DM group, which was significantly reduced in low and high dose of Ato group(dose dependent) (P<0.01),but still higher than normal control group(P<0.01). Conclusions:(1)In alloxan-induced diabetic rabbits,diabetic cardiomyopathy present at 12 weeks of diabetic duration.(2)There was impairment of left ventricular diastolic funciton at 4 weeks of diabetic duration,TDI could accurately quantify the left ventricular diastolic function of diabetic rabbits.Atorvastatin could improve left ventricular diastolic function.(3)Atorvastatin can improve the left ventricular remodeling in rabbits models of diabetes for 12 weeks,which was related to the inhibition of the overexpression of TGFβ1.